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Elucidating the neural mechanism to drive the functional recovery of dexterous hand movements after spinal cord injury by prediction error

Research Project

Project/Area Number 19H01011
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 46:Neuroscience and related fields
Research InstitutionKyoto University

Principal Investigator

Isa Tadashi  京都大学, 医学研究科, 教授 (20212805)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥45,630,000 (Direct Cost: ¥35,100,000、Indirect Cost: ¥10,530,000)
Fiscal Year 2021: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Fiscal Year 2020: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Fiscal Year 2019: ¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Keywords機能回復 / 運動制御 / 脊髄損傷 / 霊長類 / 半球間抑制 / 巧緻運動 / 回路操作 / ウイルスベクター / 予測誤差 / マカクザル / 運動野
Outline of Research at the Start

中部頚髄において皮質脊髄路を損傷したサルが手指の巧緻運動を機能回復させる過程において、「損傷直後に観察される感覚運動野の高γ帯域の活動亢進」が予測誤差(運動指令の内部コピーと運動結果のフィードバックとの差)によって生じることを示す。次に、その予測誤差が計算される部位が後索系なのか小脳を介する経路なのかを感覚性視床(VPL核)及び運動性視床(VA核)からの神経活動記録によって明らかにする。そしてこの予測誤差信号が機能回復を引き起こすのに必須であることを、VPL核ないしはVA核の薬理学的機能阻害ないしはウィルスベクターを用いた経路遮断をこれら視床核から皮質感覚野への投射経路に適用することによって証明する。

Outline of Final Research Achievements

Our previous studies showed that after the partial injury of the spinal cord in monkeys, the dexterous hand movements well recovered through rehabilitative trainings. In the present study, we made extensive electrocorticography recordings from bilateral motor-related cortical areas during reach and grasp task, and found that the activity of ipsilesional premotor cortex preceding the movement onset increased during the early recovery period. To study the contribution of the interhemispheric effects from the contralesional side, we selectively blocked the callosal fibers using the double viral vector technique with DREADD, and found that the interhemisoheric inhibition before the injury turned to interhemispheric facilitation during recovery and promoted contribution of the ipsilesional premotor cortex to recovery of hand functions.

Academic Significance and Societal Importance of the Research Achievements

従来より脳卒中や脊髄損傷の患者において、障害された手と同側の皮質運動関連領野の活動が増加することが知られていたが、その意義は明らかでなかった。今回の一連の研究により、少なくとも回復初期において、障害同側運動前野の活動が、脱抑制によって、反対側皮質によってもたらされ、かつ機能回復に貢献していることが明らかになったことは、運動障害のリハビリテーション治療を体系づける上での意義は大きいと考える。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Comments on the Screening Results   Annual Research Report

Research Products

(44 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (2 results) Journal Article (17 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 16 results,  Open Access: 12 results) Presentation (18 results) (of which Int'l Joint Research: 9 results,  Invited: 12 results) Remarks (7 results)

  • [Int'l Joint Research] チュラロンコン大学(タイ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] ルーバンカトリック大学(ベルギー)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Amygdala Underlies the Environment Dependency of Defense Responses Induced via Superior Colliculus2022

    • Author(s)
      Isa Kaoru、Tokuoka Kota、Ikeda Sakura、Karimi Sara、Kobayashi Kenta、Sooksawate Thongchai、Isa Tadashi
    • Journal Title

      Frontiers in Neural Circuits

      Volume: 15 Pages: 768647-768647

    • DOI

      10.3389/fncir.2021.768647

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Double viral vector intersectional approaches for pathway-selective manipulation of motor functions and compensatory mechanisms2022

    • Author(s)
      Isa Tadashi
    • Journal Title

      Experimental Neurology

      Volume: 349 Pages: 113959-113959

    • DOI

      10.1016/j.expneurol.2021.113959

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Light Isoflurane Anesthesia on Organization of Direction and Orientation Selectivity in the Superficial Layer of the Mouse Superior Colliculus2022

    • Author(s)
      Masatoshi KASAI, Tadash ISA
    • Journal Title

      The Journal of Neuroscience

      Volume: 42 Pages: 619-630

    • DOI

      10.1523/jneurosci.1196-21.2021

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Visual instrumental learning in blindsight monkeys2021

    • Author(s)
      Kato Rikako、Zeghbib Abdelhafid、Redgrave Peter、Isa Tadashi
    • Journal Title

      Scientific Reports

      Volume: 11 Pages: 14819-14819

    • DOI

      10.1038/s41598-021-94192-7

    • NAID

      120007147049

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neural Mechanism of Blindsight in a Macaque Model2021

    • Author(s)
      Isa Tadashi、Yoshida Masatoshi
    • Journal Title

      Neuroscience

      Volume: 469 Pages: 138-161

    • DOI

      10.1016/j.neuroscience.2021.06.022

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The tectum/superior colliculus as the vertebrate solution for spatial sensory integration and action2021

    • Author(s)
      Isa Tadashi、Marquez-Legorreta Emmanuel、Grillner Sten、Scott Ethan K.
    • Journal Title

      Current Biology

      Volume: 31

    • DOI

      10.1016/j.cub.2021.04.001

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Divergent Whole Brain Projections from the Ventral Midbrain in Macaques2021

    • Author(s)
      Zubair Muhammad、Murris Sjoerd R、Isa Kaoru、Onoe Hirotaka、Koshimizu Yoshinori、Kobayashi Kenta、Vanduffel Wim、Isa Tadashi
    • Journal Title

      Cerebral Cortex

      Volume: online ahead of print Pages: 2913-2931

    • DOI

      10.1093/cercor/bhaa399

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Double viral vector technology for selective manipulation of neural pathways with higher level of efficiency and safety2021

    • Author(s)
      Koshimizu Yoshinori、Isa Kaoru、Kobayashi Kenta、Isa Tadashi
    • Journal Title

      Gene Therapy

      Volume: online ahead of print Pages: 339-350

    • DOI

      10.1038/s41434-020-00212-y

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The posterior parietal cortex contributes to visuomotor processing for saccades in blindsight macaques2021

    • Author(s)
      Kato Rikako、Hayashi Takuya、Onoe Kayo、Yoshida Masatoshi、Tsukada Hideo、Onoe Hirotaka、Isa Tadashi、Ikeda Takuro
    • Journal Title

      Communications Biology

      Volume: 4 Pages: 278-278

    • DOI

      10.1038/s42003-021-01804-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Ventral Striatum is a Key Node for Functional Recovery of Finger Dexterity After Spinal Cord Injury in Monkeys2020

    • Author(s)
      Suzuki Michiaki、Onoe Kayo、Sawada Masahiro、Takahashi Nobuaki、Higo Noriyuki、Murata Yumi、Tsukada Hideo、Isa Tadashi、Onoe Hirotaka、Nishimura Yukio
    • Journal Title

      Cerebral Cortex

      Volume: 30 Pages: 3259-3270

    • DOI

      10.1093/cercor/bhz307

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Contribution of the Pulvinar and Lateral Geniculate Nucleus to the Control of Visually Guided Saccades in Blindsight Monkeys2020

    • Author(s)
      Takakuwa Norihiro、Isa Kaoru、Onoe Hirotaka、Takahashi Jun、Isa Tadashi
    • Journal Title

      The Journal of Neuroscience

      Volume: 41 Pages: 1755-1768

    • DOI

      10.1523/jneurosci.2293-20.2020

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dexterous Hand Movements and Their Recovery After Central Nervous System Injury2019

    • Author(s)
      Isa Tadashi
    • Journal Title

      Annual review of neuroscience

      Volume: 42 Pages: 315-335

    • DOI

      10.1146/annurev-neuro-070918-050436

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neuronal and microglial localization of secreted phosphoprotein 1 (osteopontin) in intact and damaged motor cortex of macaques2019

    • Author(s)
      Sugiyama Yoko、Oishi Takao、Yamashita Akiko、Murata Yumi、Yamamoto Tatsuya、Takashima Ichiro、Isa Tadashi、Higo Noriyuki
    • Journal Title

      Brain research

      Volume: 1714 Pages: 52-64

    • DOI

      10.1016/j.brainres.2019.02.021

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The somatosensory cortex receives information about motor output2019

    • Author(s)
      Umeda Tatsuya、Isa Tadashi、Nishimura Yukio
    • Journal Title

      Science Advances

      Volume: 5 Pages: 5388-5388

    • DOI

      10.1126/sciadv.aaw5388

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamic Interaction between Cortico-Brainstem Pathways during Training-Induced Recovery in Stroke Model Rats2019

    • Author(s)
      Ishida A, Kobayashi K, Ueda Y, Shimizu T, Tajiri N, Isa T, Hida H
    • Journal Title

      Journal of Neuroscience

      Volume: 39 Pages: 7306-20

    • DOI

      10.1523/jneurosci.0649-19.2019

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Alternative routes for recovery of hand functions after corticospinal tract injury in primates and rodents2019

    • Author(s)
      Isa Tadashi、Mitsuhashi Masahiro、Yamaguchi Reona
    • Journal Title

      Current Opinion in Neurology

      Volume: 32 Pages: 836-843

    • DOI

      10.1097/wco.0000000000000749

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Difference in context-dependency between orienting and defense-like responses induced by the superior colliculus2019

    • Author(s)
      Isa Kaoru、Sooksawate Thongchai、Kobayashi Kenta、Kobayashi Kazuto、Redgrave Peter、Isa Tadashi
    • Journal Title

      bioRxiv

      Volume: 729772 Pages: 729772-729772

    • DOI

      10.1101/729772

    • Related Report
      2019 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Presentation] Dynamics of global brain networks for recovery from spinal cord injury2022

    • Author(s)
      Tadashi Isa
    • Organizer
      The 7th CiNet Conference: New horizons in brain mapping
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Induction of large-scaled adult brain plasticity for neuronal repair2022

    • Author(s)
      Tadashi Isa
    • Organizer
      The 25th Thai Neuroscience Society Conference 2022 (TNS25)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] How the brain works for recovery from spinal cord injury2021

    • Author(s)
      Tadashi Isa
    • Organizer
      Mongolian Neuroscience Society Meeting
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 盲視の脳内メカニズム  -非ヒト科霊長類を用いた研究について-2021

    • Author(s)
      伊佐 正
    • Organizer
      視覚科学フォーラム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Neural circuit mechanism of functional recovery after brain and spinal cord injury2021

    • Author(s)
      Tadashi Isa
    • Organizer
      第98回日本生理学大会 萩原生長記念レクチャー
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Massive re-routing of corticospinal projection after functional recovery from spinal cord injury in the macaque monkey2021

    • Author(s)
      Satoko Ueno, Reona Yamaguchi, Kaoru Isa, Toshinari Kawasaki, Masahiro Mitsuhashi, Tadashi Isa
    • Organizer
      第98回日本生理学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Systems neuroscience of functional recovery after brain and spinal cord Injury2020

    • Author(s)
      Tadashi Isa
    • Organizer
      1st Taiwan Society for Neuroscience Meeting (Plenary Lecture)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Massive re-routing of the corticospinal tract fibers accompanying recovery from spinal cord injury in macaque monkey2020

    • Author(s)
      Satoko Ueno, Reona Yamaguchi, Kaoru Isa, Toshinari Kawasaki, Masahiro Mitsuhashi, Tadashi Isa
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ontribution of interhemispheric pathways between the motor-related cortical areas during recovery after the corticospinal tract lesion in macaque monkeys2020

    • Author(s)
      Masahiro Mitsuhashi, Reona Yamaguchi, Toshinari Kawasaki, Satoko Ueno, Tadashi Isa
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Global disinhibition across cortical networks for recovery of hand movements after spinal cord injury2020

    • Author(s)
      Reona Yamaguchi, Toshinari Kawasaki, Zenas C Chao, Masahiro Mitsuhashi, Satoko Ueno, Tadashi Isa
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Resting-state functional connectivity with electrocorticography as a biomarker of motor recovery after spinal cord injury in macaque monkeys2020

    • Author(s)
      Toshinari Kawasaki, Reona Yamaguchi, Zenas C Chao, Masahiro Mitsuhashi, Satoko Ueno, Yukihiro Yamao, Takayuki Kikuchi, Kazumichi Yoshida, Susumu Miyamoto, Tadashi Isa
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] How does the non-conscious visuo-motor function emerge after damage to the primary motor cortex?2020

    • Author(s)
      Tadashi Isa
    • Organizer
      1st CU-KU Symposium and 4th CU-NIPS Symposium "Advances in Neuroscience Research"
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Activity of frontal network for performance of forced-choice manual response task in blindsight monkey2019

    • Author(s)
      Yusuke Yamamoto, Reona Yamaguchi, Tomohiko Takei, Zenas C. Chao, Tadashi Isa
    • Organizer
      Annual Meeting of the Society for Neuroscience
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Neural mechanisms and functions of blindsight2019

    • Author(s)
      Tadashi Isa
    • Organizer
      IBRO2019 Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cortical oscillatory network for recovery from spinal cord injury2019

    • Author(s)
      Tadashi Isa
    • Organizer
      International Symposium on Neural Oscillation 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Global disinhibition as a key mechanism for the recovery of hand functions after spinal cord injury2019

    • Author(s)
      Tadashi Isa
    • Organizer
      The 29th Annual Meeting of the Society for Neural Control of Movement
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 機能回復の脳科学2019

    • Author(s)
      伊佐 正
    • Organizer
      第3回全国在宅医療医歯薬連合会全国大会シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 基礎研究の魅力:日本神経科学学会会長から2019

    • Author(s)
      伊佐 正
    • Organizer
      第60回日本神経学会学術集会 シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Remarks] 京都大学大学院医学研究科 高次脳科学講座 神経生物学分野

    • URL

      https://nscinbiol.med.kyoto-u.ac.jp/

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Remarks] 京都大学ヒト生物学高等研究拠点 伊佐グループ

    • URL

      https://ashbi.kyoto-u.ac.jp/ja/groups/isa/

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Remarks] researchmap 伊佐正

    • URL

      https://researchmap.jp/tadashiisa/?lang=japanese

    • Related Report
      2021 Annual Research Report
  • [Remarks] 京都大学医学研究科・医学部 神経生物学

    • URL

      https://www.med.kyoto-u.ac.jp/organization-staff/research/doctoral_course/r-019/

    • Related Report
      2021 Annual Research Report
  • [Remarks] researchmap 伊佐 正

    • URL

      https://researchmap.jp/tadashiisa/?lang=japanese

    • Related Report
      2020 Annual Research Report
  • [Remarks] 京都大学医学研究科神経生物学分野

    • URL

      https://www.med.kyoto-u.ac.jp/organization-staff/research/doctoral_course/r-019/

    • Related Report
      2020 Annual Research Report
  • [Remarks] Project 01 脳・脊髄損傷からの機能回復機構

    • URL

      https://nscinbiol.med.kyoto-u.ac.jp/projects/

    • Related Report
      2019 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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